POstmastectomy radioThErapy in Node-posiTive breast cancer with or without Internal mAmmary nodaL irradiation (POTENTIAL): a study protocol for a multicenter prospective phase III randomized controlled trial

Abstract

Background Various randomized trials have demonstrated that postmastectomy radiotherapy (RT) to the chest wall and comprehensive regional nodal areas improves survival in patients with axillary node-positive breast cancer. Controversy exists as to whether the internal mammary node (IMN) region is an essential component of regional nodal irradiation. Available data on the survival benefit of IMN irradiation (IMNI) are conflicting. The patient populations enrolled in previous studies were heterogeneous and most studies were conducted before modern systemic treatment and three-dimensional (3D) radiotherapy (RT) techniques were introduced. This study aims to assess the efficacy and safety of IMNI in the context of modern systemic treatment and computed tomography (CT)-based RT planning techniques. Methods POTENTIAL is a prospective, multicenter, open-label, parallel, phase III, randomized controlled trial investigating whether IMNI improves disease-free survival (DFS) in high-risk breast cancer with positive axillary nodes (pN+) after mastectomy. A total of 1800 patients will be randomly assigned in a 1:1 ratio to receive IMNI or not. All patients are required to receive ≥ six cycles of anthracycline and/or taxane-based chemotherapy. Randomization will be stratified by institution, tumor location (medial/central vs. other quadrants), the number of positive axillary nodes (1–3 vs. 4–9 vs. ≥10), and neoadjuvant chemotherapy (yes vs. no). Treatment will be delivered with CT-based 3D RT techniques, including 3D conformal RT, intensity-modulated RT, or volumetric modulated arc therapy. The prescribed dose is 50 Gy in 25 fractions or 43.5 Gy in 15 fractions. Tiered RT quality assurance is required. After RT, patients will be followed up at regular intervals. Oncological and toxilogical outcomes, especially cardiac toxicities, will be assessed. Discussion This trial design is intended to overcome the limitations of previous prospective studies by recruiting patients with pN+ breast cancer, using DFS as the primary endpoint, and prospectively assessing cardiac toxicities and requiring RT quality assurance. The results of this study will provide high-level evidence for elective IMNI in patients with breast cancer after mastectomy. Trial registration ClinicalTrails.gov, NCT04320979. Registered 25 Match 2020, https://clinicaltrials.gov/ct2/show/NCT04320979

Effects of Radiation Dose on Liver After Free-breathing Volumetric Modulated Arc Therapy for Breast Cancer

“…Contrarily, FB-VMAT can deliver radiation dose to the breast and regional nodes without compromising RT target coverage and normal organs sparing (26,27). For breast cancer, FB-VMAT has been applied to shorten treatment courses (6,8), and reduce skin toxicity (28) and cardiac dose (7,29). At our institution, we administer FB-VMAT with the aim of hypofractionation or regional irradiation in patients with breast cancer.…”

“…Volumetric modulated arc therapy (VMAT) is a type of rotational IMRT with a faster dose delivery than static IMRT (5). The use of VMAT for breast cancer is increasing in many fields of adjuvant RT, such as hypofractionated whole breast RT (6), regional nodal irradiation (7), and simultaneous integrated boost (8).…”

Variability of Target Volumes and Organs at Risk Delineation in Breast Cancer Radiation Therapy: Quality Assurance Results of the Pretrial Benchmark Case for the POTENTIAL Trial

“…Evaluation of the enrolled cases will be assessed by experts in the QA group who can differentiate between clinically important and unimportant discrepancies. 27 The present study provided a valuable insight into the importance of pretrial target delineation QA in breast cancer RT. Nevertheless, there were some limitations in this study.…”

Adjuvant medial versus entire supraclavicular lymph node irradiation in high-risk early breast cancer (SUCLANODE): a protocol for a multicenter, randomized, open-label, phase 3 trial

“…In the context of ongoing clinical trials, the RADCOMP atlas for RTOG 3509/3510 trial has introduced the posterolateral SCL as an optional volume to consider for irradiation [ 14 ]. Additionally, a phase 3 randomized clinical trial exploring the impact of internal mammary nodal irradiation on disease-free survival in high-risk breast cancer patients in currently recruited in China, with the SCL CTV encompassing the entire SCL region [ 15 ]. However, some other clinical trials, such as NRG 9353, Alliance A11022, Danish Breast Cancer Cooperative Group (DBCG) RT Recon Trial, and DBCG HYPO II Trial still define the SCL CTV based on RTOG atlas or ESTRO guidelines.…”